Variable DPP4 expression in multiciliated cells of the human nasal epithelium as a determinant for MERS-CoV tropism.

Summary

Using human airway organoid-derived cultures and single-cell analyses, MERS-CoV was shown to infect multiciliated cells in both nasal and pulmonary epithelia, causing ciliary loss. Donor-to-donor variability in replication correlated with focal, variable DPP4 expression in the human nose, offering a mechanistic explanation for sporadic superspreading.

Key Findings

• MERS-CoV replicated to high titers in both pulmonary and nasal airway organoid-derived cultures.
• Single-cell mRNA-seq and histology showed preferential infection of multiciliated cells with loss of ciliary coverage.
• Replication efficiency varied widely between donors and correlated with focal, variable DPP4 expression in human nasal tissues.

Clinical Implications

Suggests that assessing nasal DPP4 expression or ciliated cell differentiation states could identify high-risk transmitters; reinforces the value of targeting the upper airway for interventions (vaccines, antivirals, barrier methods).

Limitations

• In vitro organoid systems may not capture full in vivo mucosal immunity and aerosol dynamics
• Donor sample sizes per experiment are not detailed in the abstract

Future Directions

Quantify DPP4 variability in population-scale nasal biopsies; evaluate whether nasal DPP4 levels predict shedding/transmission; explore modulation of ciliated cell differentiation to reduce upper-airway tropism.